L-deprenyl fails to protect mesencephalic dopamine neurons and PC12 cells from the neurotoxic effect of 1-methyl-4-phenylpyridinium ion

L-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, appears to slow down the progression of Parkinson's disease. While inhibition of MAO-B activity can account for some of the effects of this substance, the basis by which L-deprenyl slows the progression of the disease remains controversial. In recent years, a new mechanism of action has emerged that may explain the ability of L-deprenyl to increase neuronal survival. L-deprenyl has been reported to modify gene expression and protein synthesis in astrocytes and PC12 cells. In this study, we tested the ability of L-deprenyl to protect mouse mesencephalic cells from the toxicity of the I-methyl-it-phenyl pyridinium ion (MPP(+)). We exposed mouse mesencephalic cell cultures to L-deprenyl (10 mu M) and, 24 h later, to MPP(+) (2.5 mu M). On the fifth day after L-deprenyl and MPP(+) exposition, cells were washed free of drugs, and the following day they were tested for dopamine uptake, intracellular dopamine content and tyrosine hydroxylase immunoreactivity. The experiments were performed either in the presence or in the absence of glia. It was found that L-deprenyl pretreatment failed to achieve any protection against MPP(+) toxicity. The fall in dopamine uptake and intracellular dopamine content, and the diminution of tyrosine hydroxylase immunoreactivity observed in cells pretreated with L-deprenyl and then given MPP(+) were not significantly different from the values observed in cells treated with MPP(+) alone. Additional experiments performed in PC12 cells, confirmed the failure of L-deprenyl to abolish the toxicity of MPP(+). Our data seem to be at variance with previous reports demonstrating that the MAO-B inhibitor L-deprenyl protects dopaminergic neurons against MPP(+) toxicity [12,20]; furthermore they do not support alternative mechanisms of action of L-deprenyl against MPP(+) toxicity.